This invention relates to the production of daunosamine and, more particularly, to a novel synthetic route for the preparation of daunosamine hydrochloride from a D-mannose starting material.
The anthracycline antibiotics daunorubicin (daunomycin) and adriamycin, particularly the latter, have shown considerable promise as anticancer agents in clinical use. In view of the high cost of microbially producing these antibiotics, various attempts have recently been made to develop an effective synthetic route for their production. One approach, proposed by Acton et al., J. Med. Chem., 17 (1974) 659-660, involves a coupling reaction between the separately prepared amino sugar and aglycone constituents of the antibiotic.
Daunosamine (3-amino-2,3,6-trideoxy-L-lyxo-hexose) is the amino sugar constituent of both daunorubicin and adriamycin. A synthesis of daunosamine isolated as its hydrochloride by a route starting from L-rhamnose (6-deoxy-L-mannose) has been proposed by Marsh et al., Chem. Commun., (1967) 973-975. The Marsh et al., procedure, however, suffers from several drawbacks. First of all, L-rhamnose is a relatively expensive starting sugar for the preparation of daunosamine. Secondly, the route described by Marsh et al., requires several steps involving chromatographic resolution, and gives daunosamine in relatively low overall yield.